ABSTRACT
The characteristic genetic abnormality of neuroendocrine neoplasms (NENs), a heterogeneous group of tumors found in various organs, remains to be identified. Here, based on the analysis of the splicing variants of an oncogene Focal Adhesion Kinase (FAK) in The Cancer Genome Atlas datasets that contain 9193 patients of 33 cancer subtypes, we found that Box 6/Box 7-containing FAK variants (FAK6/7) were observed in 7 (87.5%) of 8 pancreatic neuroendocrine carcinomas and 20 (11.76%) of 170 pancreatic ductal adenocarcinomas (PDACs). We tested FAK variants in 157 tumor samples collected from Chinese patients with pancreatic tumors, and found that FAK6/7 was positive in 34 (75.6%) of 45 pancreatic NENs, 19 (47.5%) of 40 pancreatic solid pseudopapillary neoplasms, and 2 (2.9%) of 69 PDACs. We further tested FAK splicing variants in breast neuroendocrine carcinoma (BrNECs), and found that FAK6/7 was positive in 14 (93.3%) of 15 BrNECs but 0 in 23 non-NEC breast cancers. We explored the underlying mechanisms and found that a splicing factor serine/arginine repetitive matrix protein 4 (SRRM4) was overexpressed in FAK6/7-positive pancreatic tumors and breast tumors, which promoted the formation of FAK6/7 in cells. These results suggested that FAK6/7 could be a biomarker of NENs and represent a potential therapeutic target for these orphan diseases.
Subject(s)
Female , Humans , Alternative Splicing , Breast Neoplasms/metabolism , Carcinoma, Pancreatic Ductal/pathology , Focal Adhesion Protein-Tyrosine Kinases/therapeutic use , Nerve Tissue Proteins/genetics , Neuroendocrine Tumors/genetics , Oncogenes , Pancreatic Neoplasms/metabolismABSTRACT
Objective To investigate the expression and clinical significance of Ku70 in nasopha ryngeal oarcinoma(NPC).Methods The expression of Ku70 protein in 223 specimens of nasopharyngeal carcinoma was examined by immunohistochemistry.Based on the levels of ku70 immunoreactivities,the 223 specimens were divided into high Ku70 expression group and low Ku70 expression group.The correlation of Ku70 expression with clinicopathologic features and prognosis of NPC was analyzed according to the clinical data. Results The rate of high Ku70 expression was 63.7%.Univariate survival analysis suggested that the overall survival rate was significantly lower in high KuTO expression group than in low Ku70 expression group (X2 = 7.88,P = 0.005).Cox multivariate analysis indicated that T stage,N stage and M stage were the independent prognostic predictors (X2 = 8.02,7.22,36.86;P =0.005,0.007,0.000),but not with gender, age or pathological type(X2 = 0.08 ,1.04,2.34;P = 0.780,0.308,0.126),the influence of Ku70 on the o verall survival rate was close to critical value(P = 0.085).Conclusions Ku70 is positively expressed in the majority of NPC.KuT0 expression has significant correlations with T stage and N stage.The results of our study suggest that Ku70 is a valuable prognostic factor of NPC.
ABSTRACT
AIM: To investigate the relationship between expression of Bmi-1(B cell-specific MLV integration site-1) in gastric cancer and its clinicopathologic significance.METHODS: 146 surgical patients with gastric carcinoma were followed up at least 2 years.Expression of Bmi-1 protein was examined by immunohistochemistry in their archival paraffin embedded tissue specimens.RESULTS: The intensive positive rate of Bmi-1 expression in gastric cancer was 67.8%(99/146).Expression of Bmi-1 was highly correlated with tumor size,clinical stage,lymph node metastasis and T classification(P0.05).The survival rate in the patients with Bmi-1 expression was much lower than that in those patients without Bmi-1 expression(P